We previously described five different stage-specific cellular transforming genes activated in T-\and B-lymphoid leukemias, lymphomas and myelomas, which are evolutionarily well-conserved between mouse and man. These genes have been detected by transfection of NIH 3T3 cells and analyzed by restriction endonuclease sensitivity. A mouse T-lymphoma gene has been isolated utilizing recombinant DNA technology and is currently being characterized. The isolated clone containing the transforming sequence transforms with high efficiency and it is apparent from current efforts that the size of the gene is between 1 and 2 kilobases. This gene, when used as a molecular probe, appears to identify a small gene family. In collaboration with Dr. Geoffrey Cooper's laboratory, utilizing his chicken bursal gene as a probe, we have isolated a molecular clone containing the human B lymphoma-transforming sequence. This gene is the human analogue of the chicken bursal gene and is the activated cellular transforming gene which we detect by transfection in human African and American Burkitts lymphomas. The human B-lym gene is not homologous to c-myc, and in collaboration with Dr. Philip Leder's laboratory, has been localized to human chromosome 1. Hybridization of this gene to the mouse T-lymphoma gene indicates that they share no homology. Presently, we are continuing to isolate and characterize cellular-transforming genes from the lymphoid series and are further investigating the multistage process of carcinogenesis.